The present invention is novel compounds, which are derivatives of hydroxybenzylamine and as such are related to capsaicin. The present compounds have antiinflammatory activity for the treatment of arthritis, asthma, Raynaud's disease, inflammatory bowel disorders, trigeminal or herpetic neuralgia, inflammatory eye disorders, psoriasis, and/or having analgesic activity for the treatment of dental pain and headache, particularly vascular headache, such as migraine, cluster, and mixed vascular syndromes, as well as nonvascular, tension headache. Thus, the present invention is also a pharmaceutical composition comprising the novel compounds together with a pharmaceutically acceptable carrier or methods of use of such compounds for treatment of the above noted conditions.
Among known compounds are benzoic acid derivations in which the derivative is limited to a substituent having a (naphthoxy)isobutyramido containing group and for which compounds an antiphlogistic activity is disclosed. See U.S. Pat. No. 4,183,954. Additionally O. Exner, et al. discloses N-(4-carboxybenzyl)acetamide in "Quantitative Evaluation of the Inductive Effect," Coll. Czech. Chem. Commun. 27, 2299 (1962). But no teaching to activity or utility for the compound is indicated by Exner, et al.
Selected compounds related to capsaicin are disclosed in a series of patents. Such disclosed compounds have various amido, sulfonylamido or amidosulfonyl and thioamido linkages in combination with a benzyl or a benzyl analog moiety and may be found in U.S. Pat. Nos. 4,443,473, having a parahydroxybenzyl; 4,313,958, that has a paramethoxybenzyl and claims the use of capsaicin; U.S. Pat. Nos. 4,460,602 having a para-hydroxybenzyl; 4,401,663 having a para-hydroxy- or methoxybenzyl; European Patent Application No. 0,132,113 having a para-hydroxybenzyl; U.S. Pat. No. 4,424,203 having a para-hydroxy- or, alkyloxybenzyl; European Patent Application No. 0,132,114 having a para-hydroxy or alkoxybenzyl; European Patent Application No. 0,132,346 having a para-hydroxy or alkyloxy-benzyl and European Patent Application No. 0,132,115 having a para-hydroxybenzyl; as well as European Patent Application Nos. 0,149,544 and 0,149,545 both of which may have a para-hydroxybenzyl moiety. Of these European Patent Applications Nos. 0,132,115; 0,132,346; 0,132,113; 0,132,114; 0,132,115, 0,149,544 and 0,149,545 include a short chain acyl group on the benzyl moiety. Analgesia is disclosed as an activity for the compounds of the references. However, none of the references teach the compounds having the combination of moieties of the present invention.
Additionally, related benzoic acid and benzoic acid ester derivatives having antiinflammatory and analgesic activity are found in co-pending U.S. application Ser. No. 811,567 filed Dec. 20, 1985, and now U.S. Pat. No. 4,869,182, which refers to most of the above noted references. Therefore, U.S.S.N. No. 811,567 is hereby incorporated by reference.